Antigen-Specific FoxP3-Transduced T-Cells Can Control Established Type 1 Diabetes

Abstract

1 CD4؉ CD25 ؉ T-cells can be used to interfere with spontaneous autoimmune diseases such as type 1 diabetes. However, their low frequency and often unknown specificity represent major obstacles to their therapeutic use. Here we have explored the fact that ectopic expression of the transcription factor Foxp3 can confer a suppressor phenotype to naïve CD4 ؉ T-cells. We found that retroviral transduction of polyclonal CD4 T-cells with FoxP3 was not effective in interfering with established type 1 diabetes. Thus, more subtle and more organ-specific regulation might be required to prevent type 1 diabetes, as well as to avoid systemic immunosuppression. However, a single injection of 10

Forced overexpression of either of the two common human Foxp3 isoforms can induce regulatory T cells from CD4+CD25– cells

“…Importantly, our data demonstrate that when overexpressed, both Foxp3 isoforms are capable of converting conventional CD4 + CD25 -cells into Treg. These latter results confirm and extend the findings of three other studies in the human setting [13,15,16] and of several studies in mice [3,4,[17][18][19][20][21].…”

Reciprocal generation of Th1/Th17 and Treg cells by B1 and B2 B cells

“…Previous efforts to generate T reg cells included retroviral transduction of CD4 + T cells [20], polyclonal expansion of nT reg cells [21], and induction of iT reg cells using DC [22]. We report here that conventional B2 cells efficiently convert Foxp3 -T cells into iT reg cells, at frequencies greater than seen with DC (data not shown).…”

Treg cells in pancreatic lymph nodes: the possible role in diabetogenesis and β cell regeneration in a T1D model

“…The role of Treg cell dysfunction in the pathogenesis of autoimmune disorders including T1D is strongly supported by accumulating evidence in experimental models. 19,20,[22][23][24][25] Whether there is a distinct pattern of Treg cell deviation in T1D patients is still not clear. [35][36][37] In the studies referenced above, the numbers of Treg cells were assessed in the peripheral blood of T1D patients.…”

“…Evidence is accumulating in support of Treg cell relevance to the pathogenesis of T1D. [19][20][21][22][23][24][25] Deviations in the expression of different chemokines and their receptors, as well as trafficking patterns of the Treg cells, were demonstrated in T1D both in humans and in the NOD mouse model. [26][27][28][29][30] Data generated in this study demonstrate that the numbers of Treg cells are decreased in the PLNs of the NOD mice and that the expression of the relevant chemokines, especially SDF-1, is downregulated.…”